This research proposal describes efforts on applying the technique of molecular co-crystallization and x-ray diffraction techniques to the studies of the interaction of drugs with nucleic acids. The object of this research proposal is to elucidate the stereochemistry of drug-nucleic acid interaction and to understand the mechanisms of drug action of a wide spectrum of drugs and antibiotics which exert their pharmacological action by binding to nucleic acids. In the past four years, I, associated with Professor H. M. Sobell at the University of Rochester, have been able to co-crystallize several drugs with nucleic acid components (dinucleoside monophosphates). X-ray diffraction studies of two ethidium-dinucleoside monophosphate crystalline complexes and one 9-aminoacridine-dinucleoside monophosphate crystalline complex have allowed the direct visualization of drug-nucleic acid intercalative binding at atomic resolution. These structures demonstrate drug intercalation into Watson-Crick double helices, and have provided additional information of a general nature in understanding how ethidium and 9-aminoacridine bind to double-helical nucleic acids (DNA and RNA). I will extend this research to include anticancer drugs such as ellipticine, adriamycin and their derivatives, antiviral agents and interferon inducers such as tilorone, fluorenone and their derivatives.